Is PTPRO p.Pro436= (c.1308G>A) pathogenic?

PTPRO p.Pro436= (c.1308G>A) is classified Likely benign in PTPRO (ClinVar, No assertion criteria, 1 submitter; last evaluated 2020-09-18). Very rare (popmax 0.00659%, sas); Associated with PTPRO-related disorder.

What condition is associated with PTPRO p.Pro436= (c.1308G>A)?

PTPRO p.Pro436= (c.1308G>A) is associated with PTPRO-related disorder (ClinVar).

How common is PTPRO p.Pro436= (c.1308G>A) in the general population?

PTPRO p.Pro436= (c.1308G>A) is very rare (popmax 0.00659%, sas) (gnomAD).

PTPRO p.Pro436=

c.1308G>A · rs747588432 · VCV3032280

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00659%, sas)

Conditions

PTPRO-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.8	GERP -5.9
Overall
CADD	10.08	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00659% South Asian · 6/91,078 alleles

Filtering AF 0.00286% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00195%

Overall 0.000496% 8/1,613,930 alleles · very rare exomes 7/1,461,790 · genomes 1/152,140 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00659%	15,180
Remaining individualsnot grpmax-eligible	0.0016%	62,488
European (non-Finnish)	8.47e-05%	1,179,999

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: PTPRO
Protein: p.Pro436=
Coding: c.1308G>A
MANE Select: NM_030667
dbSNP: rs747588432
Type: single nucleotide variant
Location: chr12:15508611 (GRCh38)
Gene constraint: LOEUF 0.513 · pLI 0.17 (gnomAD)
Structure: AlphaFold pLDDT 77.55 · 2 PDB
Residue 436: the fibronectin type-iii 5 domain

Full PTPRO gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

PTPRO-related disorder

Similar variants

PTPRO p.Pro436Arg Uncertain significance ★ ⚠ same residue
PTPRO c.76-67403G>A Uncertain significance ★ same condition
PTPRO p.Ala731Thr Uncertain significance ⚠ same condition
PTPRO p.Ile365Phe Uncertain significance ⚠ same condition
PTPRO c.1891+6G>T Likely benign same condition
PTPRO c.1891+8A>T Likely benign same condition
PTPRO c.2438-10A>C Likely benign same condition
PTPRO c.2748-10T>C Likely benign same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/ptpro-p-pro436 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown